This revised renewal application seeks to extend the study of developmental trajectories of drug use and related outcomes, and to examine the effects of genetic and non-genetic factors on these trajectories, of highly informative groups of youth by conducting wave 5 and 6 assessments (representing years 10 and 12 in the longitudinal study) on three youth cohorts. This effort will continue our prospective investigation into young adulthood of the developmental pathways of drug use behaviors, including SUDs. One cohort (high-risk;n = 274;mean age in 2007 = 20.4) is at elevated risk to develop SUDs as indexed by a history of externalizing disorders (e.g., ADHD, subclinical-ADHD, ODD, and CD);the second cohort (treatment;n = 393;mean age in 2007 = 20.6) has already displayed an early onset of SUDs and also has history of externalizing disorders. A third, matched control sample (n = 190;mean age in 2007 = 20.5) is also included in the design. The study will address five specific aims: (1) collect at wave 5 and wave 6 developmentally appropriate outcome measures that reflect a) developmental trajectories of drug use behaviors, and b) developmental patterns of psychosocial functioning;(2) collect DNA samples from study participants at wave 5 and genotype a selected panel of single nucleotide polymorphisms (SNPs) and variable number tandem repeats (VNTRs) in candidate genes that are potentially associated with drug-related phenotypes;(3) investigate the relations between non-genetic factors and (a) developmental trajectories of drug use (e.g., slopes and trajectory classes of drug use and SUDs), and (b) developmental trajectories of psychosocial functioning (e.g., slopes and trajectory classes of functioning);(4) investigate the relations between genetic polymorphisms and (a) developmental trajectories of drug use (e.g., slopes and trajectory classes of drug use and SUDs), and (b) developmental trajectories of psychosocial functioning (e.g., slopes and trajectory classes of functioning);and (5) test a comprehensive model of predicting drug use and psychosocial functioning trajectories to determine the relationships of genetic with non-genetic factors and how these variables may contribute to different trajectory patterns.Project Narrative A greater understanding of the course of adolescent and young adult drug use behaviors and level of functioning can meaningfully inform prevention and treatment approaches. Also, the addition of genetic variables further strengthens our search for underlying factors that contribute to variability in developmental pathways.